Department of Obstetrics and Gynecology, University of Schleswig-Holstein, Campus Luebeck, Ratzeburgerallee 160, 23538 Luebeck, Germany.
Hum Reprod. 2012 Jan;27(1):173-82. doi: 10.1093/humrep/der368. Epub 2011 Nov 16.
The Y-box-binding protein (YB-1) is described as a potential oncogene highly expressed in tumors and associated with increased cell survival, proliferation, migration and anti-apoptotic signaling. The aim of our study was to examine the expression and role of YB-1 in human endometriosis (Eo) and its association with cell survival, proliferation and invasion.
We analyzed the gene and protein expression levels of YB-1 by quantitative real-time RT-PCR and immunoassays, respectively, in peritoneal macrophages, ovarian endometrioma and eutopic endometrial tissues/cells derived from women with (n= 120) and without (n= 91) Eo. We also evaluated the functional consequences of YB-1 knockdown in the Z12 Eo cell line by measuring cell proliferation [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromid cell proliferation assay], invasion (Matrigel invasion assay) and spontaneous and tumour necrosis factor (TNFα)-induced RANTES (regulated upon activation, normal T-cell expressed and secreted chemokine) expression and apoptosis (ELISA-based assay).
YB-1 gene and protein expression was statistically significantly higher in ovarian lesions, eutopic endometrium and peritoneal macrophages of patients with Eo in comparison with the control group. Interestingly, the strongest YB-1 expression was observed in the epithelial compartment of endometrial tissues. In the Z12 cell line, YB-1 knockdown resulted in significant cell growth inhibitory effects including reduced cell proliferation and increased rates of spontaneous and TNFα-induced apoptosis. Significantly, higher RANTES expression and decreased cell invasion in vitro were also associated with YB-1 inactivation.
High YB-1 expression could have an impact on the development and progression of Eo. This study suggests the role of YB-1 as a potential therapeutic target for Eo patients.
Y 盒结合蛋白（YB-1）被描述为一种在肿瘤中高度表达的潜在癌基因，与增加细胞存活、增殖、迁移和抗凋亡信号有关。我们研究的目的是检查 YB-1 在人类子宫内膜异位症（Eo）中的表达和作用及其与细胞存活、增殖和侵袭的关系。
我们通过定量实时 RT-PCR 和免疫测定分别分析了来自患有（n=120）和不患有（n=91）Eo 的女性的腹膜巨噬细胞、卵巢子宫内膜异位症和在位子宫内膜组织/细胞中 YB-1 的基因和蛋白表达水平。我们还通过测量 Z12 Eo 细胞系中的细胞增殖[3-（4,5-二甲基噻唑-2-基）-2,5-二苯基四唑溴化物细胞增殖测定]、侵袭（Matrigel 侵袭测定）以及自发性和肿瘤坏死因子（TNFα）诱导的 RANTES（激活后调节、正常 T 细胞表达和分泌趋化因子）表达和细胞凋亡（基于 ELISA 的测定）来评估 YB-1 敲低的功能后果。
与对照组相比，Eo 患者的卵巢病变、在位子宫内膜和腹膜巨噬细胞中 YB-1 的基因和蛋白表达均具有统计学显著差异。有趣的是，在子宫内膜组织的上皮细胞中观察到最强的 YB-1 表达。在 Z12 细胞系中，YB-1 敲低导致显著的细胞生长抑制作用，包括降低细胞增殖和增加自发性和 TNFα 诱导的细胞凋亡率。重要的是，体外 RANTES 表达增加和细胞侵袭减少也与 YB-1 失活有关。
高 YB-1 表达可能对 Eo 的发生和发展有影响。本研究表明 YB-1 作为 Eo 患者的潜在治疗靶点的作用。
